Jonathan Bush launched Athenahealth in 1997 as a network of efficient and high-quality maternity clinics. But the clinics were soon gasping for cash, largely because the billing process was pathetically slow. So Bush, now 45, hired his co-founder's brother to develop software to speed up billing.

The software, not the clinics, became the company. Today, Athenahealth, a former Inc. 500 company, is publicly held, employs almost 3,000 people, and generates $595 million a year in revenue selling cloud-based billing and medical-records services to doctors and hospitals. Bush, the cousin and nephew of Presidents George W. Bush and George H. W. Bush, respectively, has been CEO the whole time.

In the beginning, how did you tell employees you were ditching clinics for software?

I did it with a slight amount of desperation in my voice! The clinics failed because the basic backbone of a business wasn't there. So I said, we're seeking the same objective--making health care more reliable, affordable, and efficient--but we're going to focus on one step earlier in the chain, the business.

There are no refunds in investing, so there was nothing they could do about it! [Laughs] But yes, basically.

Has the growth of the company changed how you lead it?

It's changed how we do new things. A big business has more resources to experiment, but it's more resistant, too, especially when it's successful. I spend more time rallying people around new ideas, making them feel why we're going in a direction. And I make sure we give new ventures room to struggle, to try out stuff, to do badly at first.

What can startup CEOs learn from their corporate counterparts?

From the beginning, we tried to create the infrastructure the company would need later on. When we had meetings in my Jeep Wagoneer, we called it the corporate jet. More seriously, everything we did was working on building policies and processes for the future, from standing meetings to department check-ins. It's like that book The Secret: You visualize the company you want to become.

What's something you wish you had realized sooner?

In the early days, I was always on duty--I literally slept with a beeper clipped to my boxer shorts. That's one of the reasons why my wife left me! I still don't think CEOs deserve much "me" time, but that kind of hypervigilance burnt me out, it burnt my family, and it kept the company from growing up around me.

What's the least glamorous part of your job?

It all feels wonderful. But the most unglamorous? Reading everyone's quarterly reports in detail before progress meetings. During those weeks, I get up at 4 a.m. to read, and it's tough because I'm dyslexic. But as we get bigger and responsibility gets more diffuse, I need to have a microscopic familiarity with the business so I can detect change as it happens.

You invest in startups. What do you look forin their leaders?

Mojo. A sense of opportunity. Inability to give up. Brilliance. And I look for some idealistic vision. For me to get excited, the business has to show a market path toward some social good--something that scrapes a layer of lameness off the world.

Who's the natural leader at Bush family reunions?

I'm pretty much the leader. [Laughs] The last time the family got together was the Walker Cup. The natural leader was the guy who footed the bill: my cousin George Walker. He was a member of the golf club hosting it, and he rallied everyone.